TOX4 (TOX high mobility group box family member 4) is a transcriptional regulator that functions as a component of protein phosphatase 1 (PP1) complexes, particularly the PNUTS-PP1 complex 1. Its primary function involves modulating RNA polymerase II (Pol II) transcriptional regulation through facilitating C-terminal domain (CTD) dephosphorylation, which restricts pause release while promoting late elongation and transcriptional reinitiation 12. TOX4 preferentially binds PP1α and demonstrates chr14 occupancy patterns resembling those of Pol II 1. Beyond transcription, TOX4 plays a crucial role in DNA repair by promoting nonhomologous end joining (NHEJ) through its association with DNA-dependent protein kinase complexes 3. In metabolic regulation, TOX4 acts as an insulin receptor-independent regulator of hepatic glucose production, controlling gluconeogenic genes like G6PC1 and PCK1 4. During development, TOX4 is essential for T cell development, affecting thymic cellularity and CD8/CD4 ratios through regulation of proliferation and apoptosis 2. Clinically, TOX4 expression is elevated in diabetic liver tissue and represents a potential therapeutic target for type 2 diabetes 45. Additionally, genetic variants in TOX4 have been associated with alcohol-associated hepatitis risk 6.